Clarithromycin in Multiple Myeloma Induction Therapy

Multiple Myeloma Clinical Trial

— CLAIM  

Official title:

A Randomized Placebo-controlled Phase II Study of Clarithromycin or Placebo Combined With VCD Induction Therapy Prior to High-dose Melphalan With Stem Cell Support in Patients With Newly Diagnosed Multiple Myeloma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02573935
• Other study ID #: DMSG 03/14
• Secondary ID: 2014-002187-32
• Status: Terminated
• Phase: Phase 2
• First received: October 8, 2015
• Last updated: September 19, 2016
• Start date: January 2015
• Est. completion date: September 2016

Study information

• Verified date: September 2016
• Source: Aalborg Universitetshospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Health and Medicines Authority
• Study type: Interventional

Clinical Trial Summary

This study evaluates the potential synergic anti-myeloma activity of clarithromycin when combined with VCD induction therapy in patients with newly diagnosed multiple myeloma.

Description:

The survival in younger myeloma patients improved in the nineties with the introduction of high-dose melphalan with autologous stem cell support (HDT). However, all patients will eventually experience relapse after HDT and there is a need for improvement of the response after HDT. The choice of induction treatment before HDT affects the outcome after induction therapy as well as the outcome after HDT.

Clarithromycin is a macrolide antibiotic frequently utilized in the treatment of respiratory tract infections and is often used in patients with known hypersensitivity to beta-lactam antibiotic. Besides antibiotic activity, clarithromycin may exert immunomodulatory and anti-inflammatory effects. The toxicity profile of clarithromycin is favourable and the cost is very low.

Studies on cell lines have shown that clarithromycin attenuates autophagy in myeloma cells and a recent study has demonstrated that treatment with clarithromycin enhanced bortezomib-induced cytotoxicity in myeloma cells. Phase II studies without control groups have indicated that clarithromycin might enhance the effect of the thalidomide and lenalidomide. A case-matched analysis compared patients at one centre receiving clarithromycin, lenalidomide and dexamethasone with an equal number of patients at another centre receiving lenalidomide and dexamethasone. This study indicated a favourable effect of clarithromycin with a higher frequency of complete response, very-good-partial-response or better response and progression-free survival. However, there is a need for controlled studies to determine whether clarithromycin might enhance the effect of other myeloma agents.

This randomized placebo-controlled study will include 160 patients with newly diagnosed multiple myeloma eligible for HDT. The study evaluates the potential synergic anti-myeloma activity of clarithromycin when combined with VCD induction therapy in patients with newly diagnosed multiple myeloma, and is conducted by the Danish Myeloma Study Group (DMSG) at seven clinics in Denmark. The first patient was included in May 2015 and enrolment is expected to continue until October 2016. The study ends when the last included patient has been followed for two months after HDT.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 58
• Est. completion date: September 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Myeloma diagnosis according to IMWG criteria

• Treatment demanding disease

• High-dose melphalan with stem cell support scheduled as a part of the treatment

• Signed informed consent given prior to any study related activities

• Age > 18 years

Exclusion Criteria:

• Allogeneic transplantation scheduled as a part of the treatment

• Myeloma treatment prior to entry in the study, except radiotherapy, bisphosphonates/denosumab or corticosteroids for symptom control

• Concurrent disease making clarithromycin treatment unsuitable

• Positive pregnancy test (only applicable for women with childbearing potential)

• Known or suspected hypersensitivity or intolerance to clarithromycin

• Prolonged QT corrected (QTc) interval ( > 500 msec on screening ECG)

• Concurrent treatment with cabergoline, fluconazole, ketoconazole, pimozide, quetiapine, sirolimus, verapamil, tacrolimus, ergot alkaloid, simvastatin or other statins

• Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrolment, uncontrolled angina or known cardiac amyloidosis

• Severe renal dysfunction (estimated creatinine clearance <10 mL/min)

• Serious medical or psychiatric illness which, in the judgment of the investigator, would make the patient inappropriate for entry into the study

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Clarithromycin
p.o. clarithromycin 500 mg twice daily for 63 days
• Placebo
Placebo tablet twice daily for 63 days
• VCD induction therapy
Three courses of VCD (sc bortezomib 1.3 mg/sqm days 1, 4, 8, 11, iv cyclophosphamide 500 mg/sqm on days 1 and 8, and p.o. dexamethasone 40 mg days 1, 2, 4, 5, 8, 9, 11, 12 in each 21-days course)

Locations

Country	Name	City	State
Denmark	Department of Hematology, Aalborg University Hospital	Aalborg
Denmark	Department of Hematology, Aarhus University Hospital	Aarhus
Denmark	Department of Hematology, Rigshospitalet	Copenhagen
Denmark	Department of Hematology, Herlev Hospital	Herlev
Denmark	Department of Hematology, Odense University Hospital	Odense
Denmark	Department of Hematology, Roskilde Hospital	Roskilde
Denmark	Department of Hematology, Vejle Hospital	Vejle

Sponsors (2)

Lead Sponsor	Collaborator
Henrik Gregersen	Danish Myeloma Study Group

Country where clinical trial is conducted

Denmark, 

References & Publications (1)

Gay F, Rajkumar SV, Coleman M, Kumar S, Mark T, Dispenzieri A, Pearse R, Gertz MA, Leonard J, Lacy MQ, Chen-Kiang S, Roy V, Jayabalan DS, Lust JA, Witzig TE, Fonseca R, Kyle RA, Greipp PR, Stewart AK, Niesvizky R. Clarithromycin (Biaxin)-lenalidomide-low-dose dexamethasone (BiRd) versus lenalidomide-low-dose dexamethasone (Rd) for newly diagnosed myeloma. Am J Hematol. 2010 Sep;85(9):664-9. doi: 10.1002/ajh.21777. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of number of participants with very good partial response or better response after three courses of VCD combined with clarithromycin or placebo		10 weeks	No
Secondary	Comparison of number of participants with very good partial response or better response after HDT in patients treated with three courses of VCD combined with clarithromycin or placebo		Five months	No
Secondary	Comparison of number of participants with sCR, CR, PR, PD or SD in the treatment groups after induction therapy and HDT, respectively		Five months	No
Secondary	Comparison of frequency of infections in patients treated VCD combined with clarithromycin or placebo		9 weeks	No
Secondary	Comparison of number of stem cells harvested in patients treated with clarithromycin and placebo in combination with VCD		Three months	No
Secondary	Neurotoxicity assessed by FACT/GOG-Ntx, Version 4.0		Five months	No
Secondary	Quality of life assessed by EORTC QLQ-MY20		Five months	No
Secondary	Quality of life assessed by EORTC QLQ-C30		Five months	No
Secondary	Comparison of adverse events in patients treated VCD combined with clarithromycin or placebo assessed by CTCAE v4.0		Three months	No